Diabetic retinopathy (DR) is a severe chronic complication of diabetes mellitus and the leading cause of blindness among working adults in the Western world.
1 Diabetic retinopathy also is associated with an increased risk of cardiovascular disease
2,3 and all-cause mortality
3 in diabetic subjects. Although poor glycemic control and longer duration of diabetes are strong risk factors, genetic factors also have been recognized as contributing to the development and progression of DR.
4
Inflammation has a critical role in the development of the early and late stages of DR.
5,6 Tumor necrosis factor (TNF), formerly called TNF-α, is a proinflammatory cytokine that promotes the upregulation of adhesion molecule expression, leukocyte recruitment, apoptosis induction, and monocyte chemo-attraction. It also is responsible for the amplification of the immune response through stimulation of the expression of various transcription factors, growth factors, and other inflammatory mediators.
5 Experimental studies in diabetic animals have shown that TNF is involved in capillary degeneration, pericyte loss, and permeability, which all are characteristic of DR.
6 Levels of TNF are increased in the retinas or vitreous humor of diabetic animals and patients. Moreover, the vitreal and serum concentrations of TNF are higher in diabetic subjects with DR or proliferative DR (PDR) than in controls.
6,7 Similarly, serum levels of soluble TNF receptors 1 and 2 are highly correlated with the severity of DR in subjects with type 2 diabetes.
8
Recently, the −238G>A polymorphism in the gene encoding TNF (
TNF) was associated with the serum levels of TNF in Eastern Indians with prediabetes
9 and with the progression of prediabetes to type 2 diabetes in Eastern Indians,
9 and PDR in Bengali Hindu.
10 The −308G>A polymorphism was associated with the progression of impaired glucose tolerance to type 2 diabetes in Finns,
11 type 2 diabetes in Asians,
12,13 macrovascular complications in Scandinavians,
14 and renal disease in Poles and Chinese with diabetes.
15,16 In the Japanese population, the −857C>T polymorphism was associated with insulin resistance,
17 type 2 diabetes,
18 and carotid plaque formation in subjects with type 2 diabetes.
19 Therefore, these findings prompted us to test the hypothesis that the −238G>A (rs361525), −308G>A (rs1800629), and −857C>T (rs1799724) polymorphisms in the
TNF gene are associated with DR in Caucasian Brazilians with type 2 diabetes.